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NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma

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Current Medical Science 2024年第1期44卷 168-179页

作者： Wei XUE Ting WANG Wen-jing tian si-qi PANG Hua-feng ZHANG Wei-dong jia Department of General Surgery The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Health and Medicine Hefei Comprehensive National Science CenterHefei 230601China The Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China

Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely unknown.The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC management.Methods Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol.RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)cells.The upregulated genes were analyzed by GO and KEGG analyses.Then,qPCR and Western blotting were employed to determine the relative gene expression levels.Afterwards,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow cytometry.Results PLC-LR and Hep3B-LR were established.There was a total of 116 significantly upregulated genes common to both LR cell lines.The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species pathways.Notably,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib resistance.The high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the apoptosis.The combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR cells.Conclusion The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.

关键词： hepatocellular carcinoma lenvatinib resistance NAD(P)H quinone oxidoreductase 1 reactive oxygen species apoptosis dicoumarol

Rogue wave solutions and rogue-breather solutions to the focusing nonlinear Schr?dinger equation

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Communications in Theoretical Physics 2024年第3期76卷 33-41页

作者： si-jia Chen Xing Lü College of Science Tianjin University of TechnologyTianjin 300384People's Republic of China Department of Mathematics Beijing Jiaotong UniversityBeijing 100044People's Republic of China Beijing Laboratory of National Economic Security Early-warning Engineering Beijing Jiaotong UniversityBeijing 100044People's Republic of China

Based on the long wave limit method,the general form of the second-order and third-order rogue wave solutions to the focusing nonlinear Schr?dinger equation are given by introducing some arbitrary parameters.The interaction solutions between the first-order rogue wave and one-breather wave are constructed by taking a long wave limit on the two-breather solutions.By applying the same method to the three-breather solutions,two types of interaction solutions are obtained,namely the first-order rogue wave and two breather waves,the second-order rogue wave and one-breather wave,respectively.The influence of the parameters related to the phase on the interaction phenomena is graphically demonstrated.Collisions occur among the rogue waves and breather waves.After the collisions,the shape of them remains unchanged.The abundant interaction phenomena in this paper will contribute to a better understanding of the propagation and control of nonlinear waves.

关键词： nonlinear Schrodinger equation rogue wave solutions interaction solutions

New method for multibody dynamics based on unknown constraint force

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Science China(Technological Sciences) 2024年第3期67卷 791-808页

作者： tian Ying jia YingHong ZHANG Jun School of Astronautics Beihang UniversityBeijing 100191China Beijing Institute of Control Engineering Beijing 100190China National Laboratory of Space Intelligent Control Beijing 100190China

This paper presents a new method for the dynamics of multibody systems based on unknown constraint force. The method can uniformly solve multibody systems with typical configurations, including the system with rigid-flexible coupling, the system in tree topology, and the system with loop constraints. Unlike common methods, the proposed method can model the loop system without “cutting off” loop constraints, leading to the exact same modelling process as the tree-like system performs. Based on graph theory, a topological record matrix M_(rec) is proposed to capture the arbitrary system configuration. Moreover, constraint forces are selected as the key variables in semi-recursive framework. With the recursive kinematics relationship between adjacent bodies, the constraint force equation is further assembled to achieve the full-state system solution. The numerical simulations demonstrate the accuracy of the proposed method.

关键词： multibody system dynamic modelling rigid-flexible coupling unknown constraint force graph theory semi-recursive algorithm

The noise spectral characteristics and noise reduction schemes of screw air-source heat pump:A case study

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Building simulation 2024年第1期17卷 53-70页

作者： Dongsheng Liu Yaohan Feng Jikang jia Pengfei si Ya Feng China Southwest Architecture Design and Research Institute Co.Ltd. Chengdu 610041China CSCEC Green Construction Engineering Research Center Chengdu 610041China

The screw air-source heat pump can cause incessant high noise levels during operation,which might hinder adoption of this energy-efficient heat pump.First,acoustic measurements and comparison testing were performed in this research.The measurements revealed that the compressor is the main noise source of the heat pump,and it shows a multipeak frequency distribution and a wide frequency spectrum under different work conditions,with multiple peaks at 63,250,and 1000 Hz.Then,a compressor sound insulation cover with broadband absorption was proposed,and it was experimentally proven that the insulation cover can reduce the maximum sound pressure level of one unit from 89.8 dBA to 79.1 dBA.Third,we proposed several noise reduction strategies and compared their noise reduction effects using computer simulation.The results showed that the noise problem can be effectively improved through the rational design of the sound barrier and the layout and opening options of heat pump.The distance between the sound barrier and heat pump and the sound attenuation due to diffraction ALa exhibit a U-shaped relation.For buildings of different heights,the optimal heights of noise barrier are proposed.The 5.5-meter is the optimal height of the sound barrier for single-story buildings.The conclusions can be applied to other building projects for heat pump noise reduction.

关键词： acoustic simulation broadband noise noise reduction air-source heat pump sound barrier

Prognostic factors associated with gastrointestinal dysfunction after gastrointestinal tumor surgery:A meta-analysis

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1420-1429页

作者： jia Song Cong Zhou tian Zhang Department of Operating Room The Fourth Affiliated Hospital of Nanjing Medical UniversityNanjing 210031Jiangsu ProvinceChina Department of Gastrointestinal Surgery Tongji Hospital of Huazhong University of Science and TechnologyWuhan 430073Hubei ProvinceChina Department of Disinfection Supply Center The Fourth Affiliated Hospital of Nanjing Medical UniversityNanjing 210031Jiangsu ProvinceChina

BACKGROUND Explore the risk factors of gastrointestinal dysfunction after gastrointestinal tumor surgery and to provide evidence for the prevention and intervention of gastrointestinal dysfunction in patients with gastrointestinal tumor surgery.AIM To investigate the potential risk factors for gastrointestinal dysfunction following gastrointestinal tumor surgery and to present information supporting the prevention and management of gastrointestinal dysfunction in surgery patients.METHODS Systematically searched the relevant literature from PubMed,Web of Science,Cochrane Library,Embase,CNKI,China Biomedical Database,Wanfang Database,and Weipu Chinese Journal Database self-established until October 1,2022.Review Manager 5.3 software was used for meta-analysis after two researchers independently screened literature,extracted data,and evaluated the risk of bias in the included studies.RESULTS A total of 23 pieces of literature were included,the quality of which was medium or above,and the total sample size was 43878.The results of meta-analysis showed that the patients were male(OR=1.58,95%CI:1.25-2.01,P=0.002)and≥60 years old(OR=2.60,95%CI:1.76-2.87,Psical index≥25.3 kg/m2(OR=1.6,95%CI:1.00-1.12,P=0.040),smoking history(OR=1.89,95%CI:1.31-2.73,Psite(OR=1.2,95%CI:1.40-2.62,Psion grade(OR=2.52,95%CI:1.90-3.56,Psion(OR=2.92,95%CI:0.88-9.73,P=0.010)is a risk factor for postoperative gastrointestinal dysfunction in patients with gastrointestinal tumors.CONCLUsiON There are many factors affecting gastrointestinal dysfunction in gastrointestinal patients

关键词： Gastrointestinal tumor surgery Postoperative gastrointestinal dysfunction Intestinal paralysis Risk factors Metaanalysis

Parsing Objects at a Finer Granularity: A Survey

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Machine Intelligence Research 2024年第3期21卷 431-451页

作者： Yifan Zhao jia Li Yonghong tian School of Computer Science Peking UniversityBeijing100871China State Key Laboratory of Virtual Reality Technology and Systems School of Computer Science and EngineeringBeihang UniversityBeijing100191China

Fine-grained visual parsing, including fine-grained part segmentation and fine-grained object recognition, has attracted considerable critical attention due to its importance in many real-world applications, e.g., agriculture, remote sensing, and space technologies. Predominant research efforts tackle these fine-grained sub-tasks following different paradigms, while the inherent relations between these tasks are neglected. Moreover, given most of the research remains fragmented, we conduct an in-depth study of the advanced work from a new perspective of learning the part relationship. In this perspective, we first consolidate recent research and benchmark syntheses with new taxonomies. Based on this consolidation, we revisit the universal challenges in fine-grained part segmentation and recognition tasks and propose new solutions by part relationship learning for these important challenges. Furthermore, we conclude several promising lines of research in fine-grained visual parsing for future research.

关键词： Finer granularity visual parsing part segmentation fine-grained object recognition part relationship.

Acupuncture for obesity and related diseases:Insight for regulating neural circuit

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Journal of Integrative Medicine 2024年第2期22卷 93-101页

作者： Lin-yan jiang Jun tian Ya-nan Yang Shao-hui jia Qing Shu Department of Rehabilitation Medicine Zhongnan HospitalWuhan UniversityWuhan 430071Hubei ProvinceChina School of Sports Medicine Wuhan Sports UniversityWuhan 430079Hubei ProvinceChina Department of Traditional Chinese Medicine China Resources&Wu Gang General HospitalWuhan 430080Hubei ProvinceChina

Obesity is defined as abnormal or excessive fat accumulation that may impair health.Obesity is associated with numerous pathological changes including insulin resistance,fatty liver,hyperlipidemias,and other obesity-related diseases.These comorbidities comprise a significant public health threat.Existing anti-obesity drugs have been limited by side effects that include depression,suicidal thoughts,cardiovascular complications and stroke.Acupuncture treatment has been shown to be effective for treating obesity and obesity-related conditions,while avoiding side effects.However,the mechanisms of acupuncture in treating obesity-related diseases,especially its effect on neural circuits,are not well understood.A growing body of research has studied acupuncture’s effects on the endocrine system and other mechanisms related to the regulation of neural circuits.In this article,recent research that was relevant to the use of acupuncture to treat obesity and obesity-related diseases through the neuroendocrine system,as well as some neural circuits involved,was summarized.Based on this,acupuncture’s potential ability to regulate neural circuits and its mechanisms of action in the endocrine system were reviewed,leading to a deeper mechanistic understanding of acupuncture’s effects and providing insight and direction for future research about obesity.

关键词： Obesity Acupuncture Neural circuit Appetite Energy metabolism

single-cell profiling of the pig cecum at various developmental stages

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Zoological Research 2024年第1期45卷 55-68页

作者： Yan-Yuan Xiao Qing Zhang Fei Huang Lin Rao tian-Xiong Yao si-Yu Yang Lei Xie Xiao-Xiao Zou Li-Ping Cai jia-Wen Yang Bin Yang Lu-Sheng Huang National Key Laboratory for Swine Genetic Improvement and Germplasm Innovation Ministry of Science and Technology of ChinaJiangxi Agricultural UniversityNanchangJiangxi 330045China

The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.

关键词： single-cell RNA-seq Cecum Bama Xiang pigs Various developmental stages Cellular heterogeneity

Artificial intelligence optimization and controllable slow-release iron sulfide realizes efficient separation of copper and arsenic in strongly acidic wastewater

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Journal of Environmental Sciences 2024年第5期139卷 293-307页

作者： Xingfei Zhang Chenglong Lu jia tian Liqiang Zeng Yufeng Wang Wei Sun Haisheng Han jianhua Kang School of Minerals Processing and Bioengineering Central South UniversityChangsha 410083China Centre for Mined Land Rehabilitation Sustainable Minerals InstituteThe University of QueenslandBrisbane 4072Australia

Iron sulfide(FeS)is a promising material for separating copper and arsenic from strongly acidic wastewater due to its S^(2-)slow-release effect.However,uncertainties arise because of the constant changes in wastewater composition,affecting the selection of operating parameters and FeS types.In this study,the aging method was first used to prepare various controllable FeS nanoparticles to weaken the arsenic removal ability without affecting the copper removal.Orthogonal experiments were conducted,and the results identified the Cu/As ratio,H_(2)SO_(4) concentration,and FeS dosage as the three main factors influencing the separation efficiency.The backpropagation artificial neural network(BP-ANN)model was established to determine the relationship between the influencing factors and the separation efficiency.The correlation coefficient(R)of overall model was 0.9923 after optimizing using genetic algorithm(GA).The BP-GA model was also solved using GA under specific constraints,predicting the best solution for the separation process in real-time.The predicted results show that the high temperature and long aging time of FeS were necessary to gain high separation efficiency,and the maximum separation factor can reached 1,400.This study provides a suitable sulfurizing material and a set of methods and models with robust flexibility that can successfully predict the separation efficiency of copper and arsenic from highly acidic environments.

关键词： FeS nanoparticles Aging Sulfide precipitation Orthogonal experiment Artificial neural network Prediction